Multiple sclerosis (MS) is considered to be an autoimmune disease mediated
by T cells reactive with Ags in the CNS.

Therefore, it has been postulated
that neuroantigen-reactive T cells bearing particular types of TCRs are
expanded clonally during the course of the disease.

However, there is a
controversy with regard to the TCR usage by T cells associated with the
development of MS.

By the use of complementarity-determining region 3 spectratyping
analysis that is shown to be a useful tool for identification of pathogenic
TCR in autoimmune disease models, we tried to demonstrate that spectratype
was T cells bearing particular types of TCR are activated in MS patients.

Consequently, it was found that Vbeta5.2 were often oligoclonally expanded
in peripheral blood of MS patients, but not of healthy subjects.

Sequence
analysis of the complementarity-determining region 3 region of spectratype-derived
TCR clones revealed that the predominant TCR clone was different from patient
to patient, but that similar results were obtained in a patient examined
at different time points.

More importantly, examination of cerebrospinal
fluid T cells and longitudinal studies of PBLs from selected patients revealed
that Vbeta5.2 expansion was detectable in the majority of patients examined.

These findings suggest that Vbeta5.2 spectratype expansion is associated
with the development of MS and that TCR-based immunotherapy can be applicable
to MS patients if the TCR activation pattern of each patient is determined
at different stages of the disease.